Establishment of Hippo pathway defective oral cancer model mouse
| Project/Area Number |
18K15240
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Kobe University |
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Principal Investigator |
Ueda Fumihito 神戸大学, 医学研究科, 学術研究員 (20806129)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Hippo経路 / HNSCC / マウスモデル / YAP1 / モデル動物 |
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| Outline of Final Research Achievements |
Although some genetic abnormalities are reported in patients with Head-and-neck squamous cell carcinoma (HNSCC), other genetic mutations may also be important for onset and progression of HNSCC because these reported mutations cannot reproduce tumorigenesis for short span. Here, we established HNSCC model mouse by tongue-specific deletion of Hippo pathway gene, underwent surprisingly rapid and highly reproducible tumorigenesis. Combinations of molecules mutated in HNSCC may increase and sustain YAP1, effector of Hippo pathway activation to the point of oncogenicity. Strikingly, siRNA or pharmacological inhibition of YAP1 blocks murine HNSCC onset in vitro and in vivo. Our present data indicating that YAP1 may be a strong driver of the onset and progression of HNSCC.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトの全悪性腫瘍の半数以上でHippo経路異常をみること、種々の組織におけるHippo経路の単独異常で非常に早期にまた高効率に腫瘍形成をみることから、Hippo経路の機能・制御解析は、世界的に注目されつつあるテーマである。
口腔におけるHippo経路の生理的意義や破綻病態を明らかにする本研究は、生理学、生化学、腫瘍学等の研究分野へ新しい知見を与える。またこれまで原因が多岐にわたり治療が困難であった頭頚部扁平上皮がん(HNSCC)の共通発症・進展機構が解明されることのみならず、HNSCCの新治療法やその効果も提示し、臨床医学や国民福祉に大きく貢献する。
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Report
(3 results)
Research Products
(1 results)
